Objective To develop RNA splicing biomarkers of disease severity and therapeutic response in myotonic dystrophy type 1 (DM1) and type 2 (DM2). Methods In a discovery cohort we used microarrays to perform global analysis of alternative splicing in DM1 and DM2. The newly identified splicing changes were combined with previous data to create a panel of 50 putative splicing defects. In a validation cohort of 50 DM1 subjects we measured the strength of ankle dorsiflexion (ADF) and then obtained a needle biopsy of tibialis anterior (TA) to analyze splice events in muscle RNA. The specificity of DM-associated splicing defects was assessed in disease controls. The CTG expansion size in muscle tissue was determined by Southern blot. The reversibility of splicing defects was assessed in transgenic mice by using antisense oligonucleotides (ASOs) to reduce levels of toxic RNA. Results Forty-two splicing defects were confirmed in TA muscle in the validation cohort. Among these, 20 events showed graded changes that correlated with ADF weakness. Five other splice events were strongly affected in DM1 subjects with normal ADF strength. Comparison to disease controls and mouse models indicated that splicing changes were DM-specific, mainly attributable to MBNL1 sequestration, and reversible in mice by targeted knockdown of toxic RNA. Splicing defects and weakness were not correlated with CTG expansion size in muscle tissue. Interpretation Alternative splicing changes in skeletal muscle may serve as biomarkers of disease severity and therapeutic response in myotonic dystrophy.

Hole‐transporting materials (HTMs) play a critical role in realizing efficient and stable perovskite solar cells (PVSCs). Considering their capability of enabling PVSCs with good device reproducibility and long‐term stability, high‐performance dopant‐free small‐molecule HTMs (SM‐HTMs) are greatly desired. However, such dopant‐free SM‐HTMs are highly elusive, limiting the current record efficiencies of inverted PVSCs to around 19%. Here, two novel donor–acceptor‐type SM‐HTMs (MPA‐BTI and MPA‐BTTI) are devised, which synergistically integrate several design principles for high‐performance HTMs, and exhibit comparable optoelectronic properties but distinct molecular configuration and film properties. Consequently, the dopant‐free MPA‐BTTI‐based inverted PVSCs achieve a remarkable efficiency of 21.17% with negligible hysteresis and superior thermal stability and long‐term stability under illumination, which breaks the long‐time standing bottleneck in the development of dopant‐free SM‐HTMs for highly efficient inverted PVSCs. Such a breakthrough is attributed to the well‐aligned energy levels, appropriate hole mobility, and most importantly, the excellent film morphology of the MPA‐BTTI. The results underscore the effectiveness of the design tactics, providing a new avenue for developing high‐performance dopant‐free SM‐HTMs in PVSCs.

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The effect of NaCl on seed germination was due to both osmotic stress and ion toxicity for the three species. High soil salinity and a high content of Na+ in seeds may induce more seeds to remain ungerminated in S. physophora and H. ammodendron. Morphological structure and adaptation to salinity during seed germination may determine the geographical distribution of H. ammodendron and S. physophora in certain saline regions.

Introduction Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI). Methods We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging. In addition, 170 age-matched replacements were tested for the first time at study wave 2. Group differences were used to calculate practice effects after controlling for attrition effects. MCI diagnoses were generated from practice-adjusted scores. Results There were significant practice effects on most cognitive domains. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%. Importantly, practice effects were present although there were declines in uncorrected scores. Discussion Accounting for practice effects is critical to early detection of MCI. Declines, when lower than expected, can still indicate practice effects. Replacement participants are needed for accurately assessing disease progression.

Enhancing nitrogen use efficiency (NUE) in crop plants is an important breeding target to reduce excessive use of chemical fertilizers, with substantial benefits to farmers and the environment. In Arabidopsis (Arabidopsis thaliana), allocation of more NO 3 2 to shoots was associated with higher NUE; however, the commonality of this process across plant species have not been sufficiently studied. Two Brassica napus genotypes were identified with high and low NUE. We found that activities of V-ATPase and V-PPase, the two tonoplast proton-pumps, were significantly lower in roots of the high-NUE genotype (Xiangyou15) ] S:R ratios were significantly higher in Xiangyou15. BnNRT1.5 expression was higher in roots of Xiangyou15 compared with 814, while BnNRT1.8 expression was lower. In both B. napus treated with proton pump inhibitors or Arabidopsis mutants impaired in proton pump activity, vacuolar sequestration capacity (VSC) of NO 3 2 in roots substantially decreased. Expression of NRT1.5 was up-regulated, but NRT1.8 was down-regulated, driving greater NO 3 2 long-distance transport from roots to shoots. NUE in Arabidopsis mutants impaired in proton pumps was also significantly higher than in the wild type col-0. Taken together, these data suggest that decrease in VSC of NO 3 2 in roots will enhance transport to shoot and essentially contribute to higher NUE by promoting NO 3 2 allocation to aerial parts, likely through coordinated regulation of NRT1.5 and NRT1.8.

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Metal selenides have great potential for electrochemical energy storage, but are relatively scarce investigated. Herein, a novel hollow core-branch CoSe nanoarray on carbon cloth is designed by a facile selenization reaction of predesigned CoO nanocones. And the electrochemical reaction mechanism of CoSe in supercapacitor is studied in detail for the first time. Compared with CoO, the hollow core-branch CoSe has both larger specific surface area and higher electrical conductivity. When tested as a supercapacitor positive electrode, the CoSe delivers a high specific capacitance of 759.5 F g at 1 mA cm , which is much larger than that of CoO nanocones (319.5 F g ). In addition, the CoSe electrode exhibits excellent cycling stability in that a capacitance retention of 94.5% can be maintained after 5000 charge-discharge cycles at 5 mA cm . An asymmetric supercapacitor using the CoSe as cathode and an N-doped carbon nanowall as anode is further assembled, which show a high energy density of 32.2 Wh kg at a power density of 1914.7 W kg , and maintains 24.9 Wh kg when power density increased to 7354.8 W kg . Moreover, the CoSe electrode also exhibits better oxygen evolution reaction activity than that of CoO.